The principle of hybridization serves as the basis upon which methods of detecting nucleic acids is founded. Conventional methods for detecting the presence of a particular nucleic acid sequence involves employing a complementary sequence, the probe sequence which is usually labeled, and incubating this labeled sequence with the sample putatively containing the sample of interest. If the polynucleotide sequence of the target nucleic acid is complementary to the polynucleotide sequence of the probe, then the two (under suitable conditions) will hybridize. If there is hybridization, then the hybridization complex can be detected. Variations of this general protocol have been developed over time. Sensitivity of the detection assay is critical especially when detecting the presence of nucleic acids that are in low concentrations.
To improve the sensitivity in nucleic acid assays, different methods of amplification have developed. One approach is to amplify the number of target molecules. Polymerase Chain Reaction, or PCR, is such a method that is employed to increase the copy number of a target polynucleotide sequence which results in the amplification of the original target sequence. Ausubel, F. M., et al. (eds.), Current Protocols in Molecular Biology, Green Publishing Associates and Wiley-Interscience, 5.sup.th ed., (1991), vol. 2, pp. 15.1.1-15.3.8.; 15.4.1-15.4.6. Strand Displacement Amplification (SDA) and Transcription Mediated Amplification (TMA) are two other examples of methods that are used to increase or amplify the target polynucleotide sequence. All of these methods require proteins, for example, the enzymes that are used in these procedures to catalyze the necessary reactions, which constrain the conditions under which the assay can be performed. Due to the necessary presence of these enzymes in these particular assays, critical and stringent reactions must be established and maintained to insure the efficacy of these stated methods.
It would be desirable to have a nucleic acid hybridization assay that is sensitive enough to amplify a signal that is generated during a hybridization-displacement assay rather than the target sequence itself, yet avoids the above-mentioned complications.